单胺转运体可以调节胞外单胺类神经递质的浓度，是目前抗抑郁药物研发的重要靶标。在前期研究中，我们发现理气类中药预知子的提取物具有和艾司西酞普兰相似的抗抑郁作用。其主要活性成分常春藤皂苷元与单胺递质（5-HT, NE, DA）转运体有很高的亲和力，抑制三种单胺递质的再摄取，从而增强突触间隙中三种单胺递质的作用，改善抑郁样行为。但是常春藤皂苷元类似物抑制单胺递质再摄取的构效关系不清楚。本项目以预知子为研究对象，利用制备HPLC/LC-MS/NMR去重复分析技术和现代分离纯化手段，开展以三萜类化合物为主的化学成分研究。评价全部化合物与单胺递质（5-HT、NE和DA）转运体的亲和力及其抑制单胺递质再摄取的能力，并结合结构修饰的手段探讨构效关系。选择抑制活性显著的化合物，通过慢性温和性不可预知应激抑郁模型进行药效学评价和初步作用机制分析，为发现新型抗抑郁活性化合物奠定基础。

Monoamine transporter, regulating the concentration of extracellular monoamine neurotransmitters, is an important target in the antidepressant drug research and development. In previous study, we found that the crude extract of Akebiae Fructus, a Qi TCM, showed the similar antidepressant activity to that of escitalopram. The main component, hederagenin, showed high affinity to monoamine (5-HT, NE, DA) transporter, and inhibited the uptake of corresponding neurotransmitter, which in turn increased the concentration of monoamine neurotransmitter in the synaptic cleft and ameliorated the depressant like behaviors. However, the structure relationship between hederagenin and monoamine uptake inhibition is not clear. This project is designed to carry out the phytochemical investigation of Akebiae Fructus by preparative HPLC/LC-MS/NMR dereplication method and modern purification technologies. All the compounds isolated are evaluated for binding affinity to monoamine transporter and monoamine uptake inhibition activity, followed by structure modification and SAR analysis. Therafter, the active compound is chosen for in vivo antidepressant activity evaluation and preliminary mechanism analysis using chronic unpredictable mild stress induced depression model, which lays a solid basis for antidepressant agent discovery.